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Effect of human umbilical cord blood-mesenchymal stem cells on cisplatin-induced nephrotoxicity in rats

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Abstract

Background

Cisplatin-containing regimen is an effective treatment for several malignancies. However, cisplatin is an important cause of nephrotoxicity. So, many trials were performed to transplant stem cells systemically or locally to control cisplatin-induced nephrotoxicity. Stem cell therapeutic effect may be dependent on the regulation of inflammation and oxidant stress.

Aim

To investigate the effect of human umbilical cord blood-mesenchymal stem cells (hUCB-MSCs) on the histological structure, the oxidant stress, and the inflammatory gene expression in an experimental model of cisplatin-induced nephrotoxicity in rats.

Method

The rats were divided into 6 equal groups (each of 10 rats): Group I included normal rats that received no treatment. Group II included healthy rats that received IV hUCB-MSCs. Group III included untreated cisplatin-induced nephrotoxic rats. Group IV included cisplatin-induced nephrotoxic rats that received magnesium (Mg) injections after injury. Group V was injected with hUCB-MSCs after injury. Group VI received both Mg and hUCB-MSCs after injury. In tissue homogenates, reduced glutathione (GSH), superoxide dismutase (SOD), and malondialdehyde (MDA) activities were measured. Quantitative real-time-polymerase chain reaction (qRT-PCR) was performed to assess iNOS, TLR4, and NF-kB gene expression. Hematoxylin and eosin (H&E) staining was performed to study the histological structure of the kidney. Immunohistochemical staining of iNOS and NF-κB was performed, as well.

Results

Disturbed kidney functions, oxidative status, and histological structure were seen in the rats that received cisplatin. Treated groups showed improvements in kidney functions, oxidative status, and histological structure, particularly in the combined treatment group.

Conclusion

In the cisplatin-induced nephrotoxicity model, hUCB-MSCs could improve the functional and morphological kidney structure by modulation of oxidative and inflammatory status.

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SH and MMH designed the work and supervised the research. SH, AAS, AT, RS, and EMAA prepared figures, SH wrote the main manuscript text.

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Correspondence to Samia Hussein.

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The research protocol was approved by the Institutional Animal Care and Use Committee, Zagazig University (ZU-IACUC/3/F/442/2022).

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Hussein, S., Hasan, M.M., Saeed, A.A. et al. Effect of human umbilical cord blood-mesenchymal stem cells on cisplatin-induced nephrotoxicity in rats. Mol Biol Rep 51, 234 (2024). https://doi.org/10.1007/s11033-023-08958-5

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